Secondary acetylenic carbinols



United States Patent ice 3,257,465 SECONDARY ACETYLENIC CARBINOLS MortonW. Leeds, Murray Hill, and Henry L. Komarowski, Watchung, N.J.,assignors, by mesne assignments, to Cumberland Chemical Corporation, NewYork, N.Y., a corporation of Delaware No Drawing. Continuation ofapplication Ser. No. 799,453, Mar. 16, 1959. This application May 31,1963, Ser. No. 284,330

4 Claims. (Cl. 260-618) This is a continuation of application Serial No.799,453, filed March 16, 1959, now abandoned, which, in turn, is acontinuation-in-part of application Serial No. 599,918, filed July 25,1956, now abandoned.

This invention relates to unsaturated or acetylenic secondary carbinolsand to a method of making the same. More specifically, the inventionrelates to an improved method of reacting sodium acetylide with analdehyde in selective organic diluentsv or reaction media to obtain asecondary acetylenic carbinol.

It has long been known that sodium acetylide will react with aldehydesin various reaction media to form secondary acetylenic carbinols.acetylide has been reacted with aldehydes in liquid ammonia, but thepresence'of ammonia involves objectionable features which are well knownin the art. Solutions of alkali metals in liquid ammonia act as reducingagents and reduce acetylenic compounds, to the corresponding ethylenicderivatives. Further, liquid ammonia is difficult to handle; in someinstances it forms undesirable by-products; and if it is subjected toelevated temperatures and superatmospheric pressures, the reactions areadmittedly hazardous. Aldehydes have also been reacted with acetylenicGrignard reagents, and with powdered potassium hydroxide in ether, butin all instances the 'yields of secondary acetylenic carbinols were poorand commercially impractical. 4

One object of this invention is to provide an improved method ofreacting sodium acetylide with aldehydes; another object is to effectthe reaction of sodium acetylide with aldehydes in selective reactionmedia and at favorable temperatures and pressures; and a further objectis to provide a rapid and efiicient reaction for producing secondaryacetylenic carbinols in commercial yields.

In accordance With the process of the invention, an aldehyde is reactedwith a dispersion of finely divided sodium acetylide, advantageouslyconsisting mostly of particles less than 25 microns in diameter, in aselective organic liquid medium which is substantially inert withrespect to the reactants and products of reactions, under controlledtemperature condition, to produce the desired secondary carbinol. In apreferred and especially advantageous embodiment of the invention, thesodium acetylide is prepared according to the process of Patent No.2,777,884, Thomas F. Rutledge 'et al., issued Jan. 15, 1957, Process forProducing Sodium Acetylide and Improved Sodium Aoetylide Product. Thesodium acetylide thus prepared is characterized principally by being avirtually White, free flowing powder, mainly less than 5 microns indiameter, which can be melted by inert liquids without undesirablecoalescence of the particles. Since the presence of alkaline impurities,such as sodium hydroxide or metallic sodium, in the sodium acetylideinitiates undesired aldolization or aldol condensation of the aldehyde,the sodium acetylide contains less than 0.5% of such impurities forcommercially satisfactory results.

We have found that the reaction of sodium acetylide with an aldehyde canbe conducted in certain organic liquid media, to form acetyleniccarbinols in excellent yields based on the amount of aldehyde employed.

For example, sodium Patented June 21, 1966 Broadly stated, the diluentsof this invention have high dielectric constants and boiling pointsabove the reaction temperatures but well below the boiling points of thereaction products; and the diluents are relatively inert with respect tosodium acetylide, the aldehydes, and the reaction products. Further, itis believed that a medium of 7 high dielectric constant is preferredsince many reactions of sodium acetylide arev generally regarded asbeing ionic in nature. While the action of these organic diluents isdefinite, the exact manner in which they' serve is not fully understood.It may be that their action is catalytic; that some of their physicalfactors are involved, such as solubility; or that the diluents take partin the reaction in some manner. In general, the class of solvents thatare particularly useful for the present invention includes polyethers,acetals, and tertiary organic bases-all of which do not contain anyfunctional group that reacts with either the aldehyde or the sodiumacetylide. i

An especially satisfactory diluent is the cyclic ether dioxane, acolorless liquid having a melting'point of 11 C. and a boiling point of101 C. Its boiling point is well above the reaction temperatures andwell below the boiling points of the reaction products of thisinvention. Dioxane is also inert with respect to the reactants andproducts of reaction. Methylal, pyridine, and diethylene glycol dibutylether are other examples of polar materials which have been usedsatisfactorily in the practice of the present invention.

When reacting the improved sodium acetylide with an aldehyde in thepreferred reaction media, excellent yields of secondary acetyleniccarbinols are obtained according to the reaction represented by thefollowing equations: l i i i sion of sodium (in mineral oil, forexample) in a liquid such as dioxane in a reactor equipped with athermometer, heater, stirrer and acetylene inlet. Dry, purifiedacetylene is introduced into the dispersion at a temperature of from C.to 105 C. After the evolution of hydrogen has stopped, the reactionresulting in the production of sodium acetylide has been completed. Thesodium acetylide is dispersed in the dioxane in a fine state ofsubdivision, around 5 to 20 microns in diameter.

In carrying out a process of this invention, an aldehyde is added to thesuspension of sodium acetylide in one of the selective liquid media at atemperature of 30 C. to 55 C. and at such a rate as to maintain aneasily controlled reaction. After the desired reaction time, usually 1to 6 hours, the reaction is cooled to about 10 C., and water is added todecompose the salt of the carbinol. The aqueous layer of sodiumhydroxide is removed. The organic layer is separated, treated with anexcess amount of pulverized carbon dioxide, and filtered, and thesolvent and any unreacted aldehyde are separated from the carbinolformed by distillation. In view of its availability and negligible cost,water is the preferred 4 hour reaction time at the reaction temperature.The details as to the amounts of reactants, total volumes of pyridine ordiethylene glycol 'dibutyl ether, reaction temperatures, time ofreaction, and yields of carbinols based on the aldehydes are alsotabulated below.

TABLE I.REACTIONS OF ALDEHYDES WITH SODIUM AOETYLIDE Reaction MolesConditions Yield, Refrac- Ex Aldehyde Moles Sodium M1 Diluent MoleCarbmol B.P tive ROHO Acety- Percent Index,

lide Temp. Time N D 0.) (hrs.)

Formaldehyde 0. 273 0. 500 dioxane 35-37 6 96. 4 Propargyl 114-5/7G2mm 1. 4310 Propionaldehyde 1. 416 1. 416 927 dioxane 31-37 3% 86. 41-pentyn-3-o1 125l761 mm 1. 4344 n-Butyraldehyde 2. 0 2. 0 1,000 dioxane30 6 92.8 l-hexyn-3-ol. 140-1 I760 mm l. 4329 Is0butyraldehyde 1. 61 1.61 923 dioxane 35-38 5% *N.D. 4-Itt1eth3yli1-pen- 118-121/760 mm 1. 4310yn- -o Isooetylaldehyde 1. 742 1. 9 1,000 dioxane 40 4 N .D.Dtrnetztiyll-lme 112-3/30 mm 1. 4480 yn- '0 Benzaldehyde 2.0 2. 0 d080-39 5 N .D. B-phenyl-l-pro- 81-2/2 mm., 115-6/ 1. 5488 pyn-3-ol. 16mm. 7. Isobutyraldehyde. 0. 5 0. 5 500 pyridine 43-45 4 90. 04-metltiyl-t I 118121/760 m m 1. 4310 pen yn- 0 I 8 do 2. 0 2. 0 1,000pyridine... 43-45 0 88. 1 d0 118121/700 mm 1. 4310 9 Benzaldehyde 1.0 1. 0 500 pyridine..." 39-41 4 72. 8 3-phenyl-1-pro- 81-2/2 mm.,115-G/ 1. 5488 pyn-3-ol. 16 mm. 10 Isobutyraldehyde. 1. 0 1. 0 500diethylene 39-42 4% 74. 7 4-methyl-1-pen- 118-121/ 760 mm 1. 4310 glgcoldibutyl tyn-3-ol. et er. 11- Benzaldehyde 1. 0 1. 0 d0 30-33 4 74. 2 3pheny1-1-pro- 81-2/ 2 mm., 115-6/ 1. 5488 pyn-3 ol. 16 mm.

*Not determined.

Examples 1-6 A dispersion of-clean sodium metal in mineral oil,

corresponding to 1.0 mole sodium, was added to 500 ml. of purifieddioxane in a glass reactor. The reactor was fitted with a nitrogen inlettube, a water-cooled condenser the exit end of which is attached to ahydrogen analyzer, a thermometer, a mechanical stirrer, an acetylenesparger tube, and a heating mantle. While a gentle stream of drynitrogen is flowing through the reactor, heating and stirring arestarted. When the temperature of the dioxane reaches 65 C., the flow ofnitrogen is discontinued, and dried purified acetylene gas is introducedinto the dispersion at about 65 C. to 70 C. After about two hours, theevolution of hydrogen recorded by the analyzer in the exit gas streamwas less than 0.5%. The flow of acetylene was discontinued, and the mixallowed to cool to room temperature in the presence of dry nitrogen. Thesodium acetylide slurry in dioxane was charged into a- 1 liter flaskequipped with a stirrer, dropping funnel, and water cooled reflexcondenser. The size of sodium acetylide particles was less than micronsin diameter. The mixture was heated to about -55 dependingon thealdehyde used, and the aldehyde added over a period of 1 to 2 hours,followed by an additional 1 to 4 hour reaction time at the desiredtemperature. The aldehyde was added uniformly and at a preselected rateso that the heat of reaction was sufiicient to maintain the reaction ata suitable temperature without external heating. The mixture was cooledto 10 C., and then hydrolyzed with 50 ml. of cold water (10 -C.). Theorganic layer was separated, treated with an excess of pulverized carbondioxide, and filtered. For simplicity, the details as to amounts ofreactants, total volumes of dioxane, reaction temperatures, the time ofreaction, and yields of carbinols based on the aldehydes are tabulatedbelow.

Examples 7-11 In a manner similar to that described for Examples 1 to 6,finely divided sodium acetylide was prepared and separated from theother materials. It was then mixed with either pyridine or diethyleneglycol dibutyl ether; the resulting mixture was heated to about 30 to 45depending on the aldehyde used; and the aldehyde was added over a periodof 2 to 3 hours, followed by a 1 to The date in the above tableillustrates that the use of certain polar materials as the reactionmedia strongly favors the reaction between sodium acetylide and analdehyde-materials such as dioxane and pyridine which do not contain anyfunctional group that react with the aldehyde, sodium acetylide, orproducts of reaction. The

examples in the foregoing table which show the preparation of secondaryacetylenic carbinols, viz. Examples 2 to 11, and Example 12 below,illustrate the use of aldehydes of the formula RCHO wherein R is phenylor an alkyl group containing up to seven carbon atoms. Conducting theprocess at atmospheric pressures and moderate temperatures, excellentyields of secondary acetylenic carbinols are obtained in a relativelyshort period of time (4 to 6 hours). While the yields were notspecifically determined in Examples 4, 5 and 6, the conversion yieldswere 75.2%, 82.4% and 86.2%, respectively. Hence, the yields ofcarbinols would be at least as high as the conversion yields, andcomparable to the yields shown in Examples 1, 2 and 3. Generally, thesodium acetylide and aldehyde are employed in stoichiometric orequimolecular proportions, although an excess of one or the other of thereactants may be used. In all the examples, total carbinol was confirmedby standard analyses, such for example, as described by Barnes andMolinini in Anal. Chem., 27, 1025-27 (1955). It is noted from theexamples that the ratio of reactants to diluent ranges from about 1.5 to4.0 moles of reactants per liter of dioxane;

-and that commercially satisfactory yields of carbinols were obtained inall cases with the use of reaction temperatures at or near roomtemperature.

The presence of acetylene in the reaction zone favors the formation ofthe carbinol salt, and increases the carbinol yields. Commercialacetylene intended for use in the present invention is preferablydesiccated and purified, by means of absorption towers packed withAcetone is removed by passing the acetylene over activated alumina whichalso removes Water and sulfur-phosphorous compounds. Obviously theacetylene should be very soluble in the reaction medium employed.

4 Example 12 In a manner similar to that described for Examples 7 to 11,finely divided sodium acetylide was shown to react readily withacetaldehyde in a reaction medium comprising methylal. The molar ratioof sodium acety-.

lide to acetaldehyde was 111; the reaction temperature ranged from 30 to35 C.;' and 500ml. of methylal was used. Satisfactory yields of1-butyn-3-ol were obtained.

From actual tests, it was found that aldehydes do not react readily withsodium acetylide if the reaction medium is not a polar material, or ifthe reaction medium contains a functional group that reacts with thealdehyde or sodium acetylide. For example, using xylene or a mixture ofxylene and dioxane as the medium, the re; action was slow and the yieldswere significantly'decreased to as low as to 20% in some instances.

In the examples, commercially satisfactory yields of carbinols wereobtained by using sodium acetylide which is at least 99% pure, and whichhas less than 0.5%

alkalinity. In fact it extremely important that both the sodiumacetylide and the reaction medium are of very low alkalinity, since thepresence of free alkalinity in either substance initiates aldolizationof the aldehyde. Further, the sodium metal used in the preparation ofsodium dispersions should be free of superficial encrustationsordinarily found on the commercial grade of sodium. These encrustationsordinarily contain an amount of alkaline impurities which cannot betolerated in satisfactorily conducting the process of this invention.Sodium acetylide containing free sodium (the result of using sodiumdispersion containing large particles of sodium) may also result inundesired resinification of the aldehyde.

It is to be understood that the reaction should be conducted in thesubstantial absence of any substances which would interfere therewith.For example, it is preferred to exclude the oxygen in the air by eithercarrying out the reaction in the presence of an inert gas, for example,argon or helium or also nitrogen, or a mixture thereof. It has beenfound that the moisture and oxygen in the air will react with the sodiumdispersion and with sodium acetylide in a polar liquid medium.Accordingly, the various materials and reactions mentioned above shouldnot be exposed to the constituents of air and other interferingsubstances. The presence of interfering substances in any substantialamounts would adversely affect the carbinol yields.

When dioxane is intended for use in the preparation of sodium acetylideand for subsequent preparation of secondary acetylenic carbinols, it ispreferably purified. For example, technical grade of dioxane is driedover sodium hydroxide pellets for at least twenty-four hours, refluxedover sodium metal for about two hours, followed by distillation. Thecenter cut is again refluxed over fresh sodium metal for two hours,followed by distilla tion. Or the dioxane is dried over sodium hydroxidepellets, cooled to 10 C., and carefully treated with small portions of40% sodium dispersion in mineral oil until no further reaction of thesodium takes place. The dioxane is then decanted and filtered.

Technical grade methylal (assay 94-95%) contains a considerable amountof water (1.3%) and methanol (1.78%). When used in the presentinvention, it may be purified in the following manner. It is dried oversodium hydroxide pellets for 48 hours and then redistilled. The methylaldistillate (the bulk is stored over sodium hydroxide pellets) iscarefully treated with small portions of 40% sodium dispersion inmineral oil until there is no further reaction with the sodiumdispersion. The methylal is decanted, filtered and stored in suitabledry containers.

By passing technical grade diethylene'glycol dibutyl ether repeatedly (3to 4 times) through a column with molecular sieve type 4A, a pure anddry diethylene glycol dibutyl ether is obtained. The pyridine employedin the previous examples was purchased in purified form (A.C.S. reagentgrade).

Aldehydes as prepared commercially may contain impurities which wouldinterfere with the sodium acetylidealdehyde reaction, such as water,alcohol and acid.

When an aldehyde is intended for use in the present invention, it isdried over anhydrous magnesium sulfate and redistilled prior to use.These impurities, if not removed, would interfere with the reaction. Forexample, any water present inan aldehyde would react with sodiumacetylide to form sodium hydroxide which would then undesirably initiatealdolization of the aldehyde.

While the preceding examples have disclosed that sodium acetylide isreacted with specific aldehydes, it will be understood that the sodiumacetylide may be reacted with an aldehyde broadly to produce a secondaryacetylenic carbinol. The aldehydes may be aliphatic or aromatic.Representative examples of the various classes of aldehydes include thefollowing: saturated aliphatic-formaldehyde, propionaldehyde, chloral,and trifiuoroacetaldehyde; unsaturated aliphatic-crotonaldehyde andgeraniol; saturated aromat'ic-benzaldehyde, tolualdehyde, andbromobenzaldehyde; and unsaturated aromatic 5-phenylpentadien'al andcinnama'ldehyde.

Similarly, while the preceding examples have disclosed that sodiumacetylide is reacted with an aldehyde in' certain diluents such asdioxane and methylal, it will also be understood that the liquid mediumcomprises broadly any polyether, acetal, or tertiary organic base whichis inert to the reactants and products of reaction. Representativ'e'examples of satisfactory polyeth'er solvents, other than dioxane anddiethylene glycol dibutyl ether, include the following'z' ethyleneglycol diethyl ether; diethylene glycol diethyl ether; 2,3-butanedioldiethyl ether; ethylene glycol ethyl butyl ether; 4-5-dimethyl-2-propyl-1,3-dioxolane; l,l-dibutoxy-Z-ethyl hexane; l,l-dipropoxybutane;l,l-dibutoxybutane; dibutoxyphenyl methane; 1,1-

dibutoxyethane; l,l-dibutoxy-2-phenylethane; and dimethoxymethane.Representative examples of satisfactory acetal solvents other thanmethylal include: l,l-dimethoxyethane; 2-methyl-1,3-dioxolane; ethylal;and di-npropoxymethane. Representative examples of tertiary organicbases as solvents other than pyridine include substituted pyridines,quinolines and substituted quinolines. The diluents hereinabove listedhave relatively high dielectric constants, and they have boiling pointswell above the boiling points of the carbinols, which feature permitsrapid and easy separation of carbinol and diluent.

It is now readily understood that utilization of the present inventionmakes possible the production of secondary acetylenic carbinols insatisfactory yields. The process is rapid and efiicient; and theequipment is simple and inexpensive. The reaction is conducted safely,in contrast to prior art processes involving potentially hazardoussolvents such as ammonia.

The invention is not limited to the specific examples described hereinbut may be practiced in other ways without departing from the spirit andscope of the invention as defined in the appended claims.

What we claim is: Y

1. A process for preparing a secondary acetylenic carbinol whichcomprises reacting an aldehyde having the formula RCHO wherein R isphenyl or an alkyl group containing up to seven carbon atoms andfinely-divided sodium acetylide dispersed in quinoline, said sodiumacetylide being at least 99% pure and containing less than 0.5% alkalineimpurities to prevent aldolization of said aldehyde, the particles ofsaid sodium acetylide being preponderantly less than 25 microns indiameter, conducting the reaction under substantially anhydrousconditions and at a temperature of about 30 C. to about 55 C. to producethe sodium salt of said carbinol, and hydrolyzing said salt to producethe secondary acetylenic carbinol.

2. A process for preparing a secondary acetylenic carbinol whichcomprises reacting an aldehyde having the formula RCHO wherein R isphenyl or an alkyl group containing up to seven carbon atoms andfinely-divided sodium acetylide dispersed in pyridine, said sodiumacetylide being at least 99% pure and containing less than 0.5% alkalineimpurities to prevent aldolization of said aldehyde, the particles ofsaid sodium acetylide being preponderantly less than 25 microns indiameter, conducting the reaction under substantially anhydrousconditions and at a temperature of about 30 C. to about 55 C. to producethe sodium salt of said carbinol, and hydrolyzing said salt to producethe secondary acetylenic carbinol.

3. A process for preparing a secondary acetylenic carbinol whichcomprises reacting .an aldehyde having the formula RCHO wherein R isphenyl or an alkyl group containing up to seven carbon atoms andfinely-divided sodium acetylide dispersed in quinoline, said sodiumacetylide being at least 99% pure and containing less than 0.5% alkalineimpurities to prevent aldolization of said aldehyde, the particles ofsaid sodium acetylide being preponderantly less than 25 microns indiameter, conducting the reaction in a reaction zone under substantiallyanhydrous conditions and at a temperature of about 30 C. to about 55 C.to produce the sodium salt of said carbinol, maintaining an inert gasatmosphere in the reaction zone and introducing purified acetylene intocontact with said sodium acetylide, aldehyde and quinoline, during thecourse of the reaction, and hydrolyzing said salt to produce thesecondary acetylenic carbinol.

4. A process for preparing a secondary acetylenic carbinol whichcomprises reacting an aldehyde having the formula RCHO wherein R isphenyl or an alkyl group containing up to seven carbon atoms andfinely-divided sodium acetylide dispersed in pyridine,'said sodiumacetylide being at least 99% pure and containing less than 0.5% alkalineimpurities to prevent aldolization of said aldehyde, the particles ofsaid sodium acetylide being preponderantly less than 25 microns indiameter, conducting the reaction in a reaction Zone under substantiallyanhy drous conditions and at a temperature of about C. to about C. toproduce the sodium salt of said carbinol, maintaining an inert gasatmosphere in the reaction zone and introducing purified acetylene intocontact with said sodium acetylide, aldehyde and pyridine, during thecourse of the reaction, and hydrolyzing said salt to produce thesecondary acetylenic carbinol.

References Cited by the Examiner UNITED STATES PATENTS 2,125,384 8/1938Macallum 260-618 2,345,170 3/1944 Zeltner et al. 260638 2,455,05811/1948 Herman 260665 2,777,884 1/1957 Rutledge et a1. 260618 2,996,5528/1961 Blumenthal 260617 3,028,423 4/1962 Blumenthal 260533 LEON ZITVER,Primary Examiner.

1. A PROCESS FOR PREPARING A SECONDARY ACETYLENIC CARBINOL WHICHCOMPRISES REACTING AN ALDEHYDE HAVING THE FORMULA RCHO WHEREIN R ISPHENYL OR AN ALKYL GROUP CONTAINING UP TO SEVEN CARBON ATOMS AND FINELYDIVIDED SODIUM ACETYLIDE DISPERSED IN QUINOLINE, SAID SODIUM ACETYLIDEBEING AT LEAST 99% PURE AND CONTGAINING LESS THAN 0.5% ALKALINEIMPURITIES TO PREVENT ALDOLIZATION OF SAID ALDEHYDE, THE PARTICLES OFSAID SODIUM ACETYLIDE BEING PREPONDERANTLY LESS THAN 25 MICRONS INDIAMETER, CONDUCTING THE REACTION UNDER SUBSTANTIALLY ANHYDROUSCONDITIONS AND AT A TEMPERATURE OF ABOUT 30*C. TO ABOUT 55*C. TO PRODUCETHE SODIUM SALT OF SAID CARBINOL, AND HYDROLYZING SAID SALT TO PRODUCETHE SECONDARY ACETYLENIC CARBINOL.
 2. A PROCESS FOR PREPARING ASECONDARY ACTEYLENIC CARBINOL WHICH COMPRISES REACTING AN ALDEHYDEHAVING THE FORMULA RCHO WHEREIN R IS PHENYL OR AN ALKYL GROUP CONTAININGUP TO SEVEN CARBON ATOMS AND FINELY-DIVIDED SODIUM ACETYLIDE DISPERSEDIN PYRIDINE, SAID SODIUM ACETYLIDE BEING AT LEAST 99% PURE ANDCONTAINING LESS THAN 0.5% ALKALINE IMPURITIES TO PREVENT ALDOLIZATION OFSAID ALDEHYDE, THE PARTICLES OF SAID SODIUM ACETYLIDE BEINGPREPONDERANTLY LESS THAN 25 MICRONS IN DIAMETER, CONDUCTING THE REACTIONUNDER SUBSTANTIALLY ANHYDROUS CONDITIONS AND AT A TEMPERATURE OF ABOUT30*C. TO ABOUT 55*C. TO PRODUCE THE SODIUM SALT OF SAID CARBINOL, ANDHYDROLYZING SAID SALT TO PRODUCE THE SECONDARY ACETYLENIC CARBINOL.